This invention relates to compositions and methods for treating viral or cancerous skin disorders. In particular, this invention relates to pharmaceutical compositions useful for treating viral and/or cancerous skin disorders by topical administration of said compositions to the affected area.
Virus-induced skin disorders are widely known. Dermotropic viruses include poxvirus, measles virus, varicella-zoster, coxsackievirus, echovirus, herpes simplex, rubella adenovirus, papillomavirus and molluscum contagiosum. A variety of skin disordes, such as psoriasis, eczema, conjunctivitis, keratoconjunctivitis, gingivostoma, herpes labialis, herpes keratitis, genital herpes, chicken pox, shingles, milker's nodules, cowpox are therapeutically treated with compositions of this invention which comprise anti-viral agents for topical application. Further, various cancerous skin disorders such as melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi sarcoma and the like are also amenable to treatment by the topical application of compositions of this invention.
Surface active agents (surfactants) have recently been discovered as effective in reducing the infectivity of certain viruses. Particularly effective are the nonionic surfactants, those with ether or amide linkages between the hydrophilic and hydrophobic portions of the molecule. The therapeutic effect of these surfactants probably resides in their ability to interact with and dissolve the lipid-containing envelope of the virus, and in their ability to partially destroy the nucleocapsid of the virus.
When so employed, surfactants have been applied to the skin surface to contact the uppermost layer of infected cells. Because of a dilution effect, cells below the surface do not readily receive sufficient amounts of the surfactant to destroy the virus particles. Therefore, it would be beneficial to provide an adjuvant which aids in moving the surfactant or other medicament therewith to infected cells below the skin surface. A suitable such adjuvant is dimethyl sulfoxide.
Perhaps the best known of the antiviral agents are the interferons. Human interferons are known to protect cells against viral infections. Human interferons are produced by cells in reaction to the presence of specific inducers, such as viruses. They may be produced in vivo by the cells of living organisms, or they may be produced in vitro by cell cultures in response to the presence of the inducer. There are now known to be three major varieties of human interferon: leukocyte or alpha, fibroblast or beta, and immune or gamma interferon. There are also known to be several sub-varieties of human leukocyte and fibroblast interferon.
Human interferon is relatively nontoxic and nonantigenic in humans. It is also extremely effective against a broad spectrum of viruses, including herpes simplex virus, even at very low concentrations.
Various uses of interferon for its antiviral effect are known, see for example, U.S. Pat. No. 4,053,582 (Stickl) which discloses a method for treating herpes simplex infections in humans by administering attenuated fowl pox virus to the patient. The attenuated virus induces the patient to produce his own interferon. The herpetic lesions heal within a short time after induction.
U.S. Pat. Nos. 4,061,538 (Dorner et al.) and 4,184,917 (Dorner et al.) disclose a method of treating herpes simplex viral infections by administering structurally modified interferons to the patient. In these patients, the modified interferons are administered systematically to the patient.
Further, topical administration of human interferon in compositions containing antiviral surfactants has been shown to be effective in the treatment of skin disorders due to herpes simplex viral infection, see U.S. Pat. No. 4,507,281.
Tumor Necrosis Factor (TNF), an antitumor agent, was recently discovered by Carswell et al, Proc. Natl. Acad. Sci. U.S.A. Vol. 72, No. 9 pp. 3666-3670 (1975). TNF was found in the serum of mice, rats and rabbits which had been sensitized with an immunopotentiator and then treated with an endotoxin. Purified TNF, while having no toxic effect on the treated individual, exerts a potent activity against tumors transplanted into those individuals; the activity is not species specific. The advantage in having no cytotoxic effect against normal cells while having significant antitumor activity makes TNF an important candidate for the treatment of the skin manifestations of various types of cancers. Uses of TNF and related antitumor or anticancer agents are disclosed in U.S. Pat. Nos. 4,309,418; 4,447,355; 4,457,916; 4,481,137; 4,495,282 and 4,529,594. U.S. Pat. No. 4,481,137 discloses that several factors considered as promising therapeutic agents for tumors, e.g. lymphotoxin, TNF, interferon, had been obtained from reticulo-endothelial cells and that carcono-breaking factor (CBF) as a mixture containing lymphotoxin and TNF has been obtained from a culture of lymphoblasts grown in immune suppressed hamsters. Another antitumor agent called target cell lysis factor (TCLF) is disclosed in U.S. Pat. No. 4,495,282 as being comprised of lymphotoxin and human TNF.
Other anti-tumor agents useful in the practices of this invention, in addition to interferon and TNF, include the interleukins, particularly Interleukin II, see U.S. Pat. No. 4,518,584. Interleukin II which has been demonstrated to be an antitumor agent, is especially useful in the practices of this invention.
It is an object of the present invention to provide a pharmaceutical composition useful for the treatment of cancerous skin disorders such as by topical administration of said composition to the skin manifestations of such disorders.
It is another aspect of the present invention to provide a method for treating, viral and/or cancerous skin disorders by topically applied therapeutic compositions.